{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T08:33:41Z","timestamp":1771058021649,"version":"3.50.1"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.bioscientifica.com\/journals\/reuselicenceeje\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec><jats:title>Context<\/jats:title><jats:p>Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH, encoded by <jats:italic>H6PD<\/jats:italic>) cause apparent cortisone reductase deficiency (ACRD). H6PDH generates cofactor NADPH for 11\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD1, encoded by <jats:italic>HSD11B1<\/jats:italic>) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in <jats:italic>HSD11B1<\/jats:italic> cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with hypothalamic-pituitary-adrenal (HPA) axis activation and adrenal hyperandrogenism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Clinical, biochemical and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD\/CRD patients were compared to identify distinguishing characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Case 1 was compound heterozygous for R109A<jats:italic>fsX3<\/jats:italic> and a novel P146L missense mutation in <jats:italic>H6PD<\/jats:italic>. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in <jats:italic>H6PD<\/jats:italic>. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography\/mass spectrometry suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualised management.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Steroid profile analysis of a 24-h urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche and adult females with polycystic ovary syndrome (PCOS).<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-12-0628","type":"journal-article","created":{"date-parts":[[2012,11,7]],"date-time":"2012-11-07T06:46:09Z","timestamp":1352270769000},"page":"K19-K26","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":45,"title":["Novel H6PDH mutations in two girls with premature adrenarche: \u2018apparent\u2019 and \u2018true\u2019 CRD can be differentiated by urinary steroid profiling"],"prefix":"10.1093","volume":"168","author":[{"given":"G G","family":"Lavery","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Idkowiak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Sherlock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I","family":"Bujalska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J P","family":"Ride","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Saqib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M F","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S A","family":"Wudy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"De Schepper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Arlt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Krone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C H","family":"Shackleton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E A","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P M","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"5","key":"1_10588108","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1159\/000023577","volume":"53","author":"Biason-Lauber","year":"2000","journal-title":"Hormone research","ISSN":"https:\/\/id.crossref.org\/issn\/0301-0163","issn-type":"print"},{"issue":"4","key":"2_17770579","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/ng1214","volume":"34","author":"Draper","year":"2003","journal-title":"Nature genetics","ISSN":"https:\/\/id.crossref.org\/issn\/1061-4036","issn-type":"print"},{"issue":"10","key":"3_10996869","doi-asserted-by":"publisher","first-page":"3570","DOI":"10.1210\/jc.84.10.3570","volume":"84","author":"Jamieson","year":"1999","journal-title":"Journal of Clinical Endocrinology &amp; 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